Trial reportThe Journal of clinical investigation2018
Tie2 protects the vasculature against thrombus formation in systemic inflammation.
Trial report in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 134 citations in OpenAlex.
- Relationship between stress hyperglycaemic ratio (SHR) and critical illness: a systematic review.Cardiovascular diabetology · 2025Pooled it
- Major adverse cardiovascular events of vascular endothelial growth factor tyrosine kinase inhibitors among patients with different malignancy: A systemic review and network meta-analysis.Journal of the Chinese Medical Association : JCMA · 2024Pooled it
- Stress Hyperglycemia Ratio Predicts 28-Day Mortality in Patients with AMI Cardiogenic Shock: Insights from a Large-Scale Cohort.Journal of clinical medicine · 2026Article
- Review
- Distinct patterns of endothelial response to endotoxin in aged mice as compared to young mice.GeroScience · 2026Article
- Pathophysiology and Management of Sepsis-associated Acute Kidney Injury.Clinics in chest medicine · 2026Review
- CaMKKβ regulates transcription factor Elf2 gene methylation to maintain endothelial junctional barrier integrity.iScience · 2026Article
- Increased metallopeptidase activity, compromised endothelial integrity and impaired pathogen recognition revealed by transcriptomics inCurrent research in parasitology & vector-borne diseases · 2026Article
- Integrating Imaging-Derived Clinical Endotypes with Plasma Proteomics and External Polygenic Risk Scores Enhances Coronary Microvascular Disease Risk Prediction.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2026Article
- Simultaneous assessment of stress hyperglycemia ratio and glucose variability to predict all-cause mortality in sepsis patients across different glucose metabolic states: an observational cohort study with interpretable machine learning approach.International journal of surgery (London, England) · 2026Observational
- Evaluation of Endothelial Glycocalyx Damage in Neonatal Lambs With Diarrhoea: A Biomarker-Based Approach.Veterinary medicine and science · 2025Article
- Molecular Mechanisms of Sepsis-Associated Acute Kidney Injury.Journal of the American Society of Nephrology : JASN · 2025Review
- Role of Tie-2 Axis in Sepsis: A Potential Therapeutic Target.Journal of cellular and molecular medicine · 2025Review
- Integrating Imaging-Derived Clinical Endotypes with Plasma Proteomics and External Polygenic Risk Scores Enhances Coronary Microvascular Disease Risk Prediction.medRxiv : the preprint server for health sciences · 2025Article
- Thrombomodulin resistance as a novel prothrombotic pathway in COVID-19.Scientific reports · 2025Article
- Endothelial Glycocalyx Damage and Restoration Following Vascular Stent Implantation.Journal of cardiovascular translational research · 2025Review
- Disseminated intravascular coagulation.Journal of intensive care · 2025Review
- Cathepsin K cleavage of angiopoietin-2 creates detrimental Tie2 antagonist fragments in sepsis.The Journal of clinical investigation · 2025Article
- Unfractionated heparin attenuated histone-induced pulmonary endothelial glycocalyx injury through Ang/Tie2 pathway.Journal of inflammation (London, England) · 2025Article
- Association between stress hyperglycemia ratio and all-cause mortality in critically ill patients with sepsis: results from the MIMIC-IV database.European journal of medical research · 2025Observational
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Disordered coagulation contributes to death in sepsis and lacks effective treatments. Existing markers of disseminated intravascular coagulation (DIC) reflect its sequelae rather than its causes, delaying diagnosis and treatment. Here we show that disruption of the endothelial Tie2 axis is a sentinel event in septic DIC. Proteomics in septic DIC patients revealed a network involving inflammation and coagulation with the Tie2 antagonist, angiopoietin-2 (Angpt-2), occupying a central node. Angpt-2 was strongly associated with traditional DIC markers including platelet counts, yet more accurately predicted mortality in 2 large independent cohorts (combined N = 1,077). In endotoxemic mice, reduced Tie2 signaling preceded signs of overt DIC. During this early phase, intravital imaging of microvascular injury revealed excessive fibrin accumulation, a pattern remarkably mimicked by Tie2 deficiency even without inflammation. Conversely, Tie2 activation normalized prothrombotic responses by inhibiting endothelial tissue factor and phosphatidylserine exposure. Critically, Tie2 activation had no adverse effects on bleeding. These results mechanistically implicate Tie2 signaling as a central regulator of microvascular thrombus formation in septic DIC and indicate that circulating markers of the Tie2 axis could facilitate earlier diagnosis. Finally, interventions targeting Tie2 may normalize coagulation in inflammatory states while averting the bleeding risks of current DIC therapies.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.